Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Germany.
Phytother Res. 2013 Jan;27(1):86-98. doi: 10.1002/ptr.4692. Epub 2012 Apr 4.
African trypanosomiasis is still a major health problem in many sub-Saharan countries in Africa. We investigated the effects of three preparations of Panax ginseng, Panax notoginseng, isolated ginsenosides, and the polyacetylene panaxynol on Trypanosoma brucei brucei and the human cancer cell line HeLa. Hexane extracts and the pure panaxynol were toxic and at the same time highly selective against T. b. brucei, whereas methanol extracts and 12 isolated ginsenosides were significantly less toxic and showed only weak selectivity. Panaxynol was cytotoxic against T. b. brucei at the concentration of 0.01 µg/mL with a selectivity index of 858, superior even to established antitrypanosomal drugs. We suggest that the inhibition of trypanothione reductase, which is only found in trypanosomes, might explain the observed selectivity. The high selectivity together with a cytotoxic concentration in the range of the bioavailability makes panaxynol and other polyacetylenes in general very promising lead compounds for the treatment of African trypanosomiasis.
非洲锥虫病仍然是非洲撒哈拉以南许多国家的一个主要卫生问题。我们研究了三种人参制剂(人参、三七、分离的人参皂甙)和多炔panaxynol 对布氏锥虫和人宫颈癌细胞系 HeLa 的影响。己烷提取物和纯 panaxynol 具有毒性,同时对 T. b. brucei 具有高度选择性,而甲醇提取物和 12 种分离的人参皂甙的毒性则明显较低,仅显示出较弱的选择性。Panaxynol 在 0.01μg/ml 的浓度下对 T. b. brucei 具有细胞毒性,选择指数为 858,甚至优于已有的抗锥虫药物。我们认为,仅在锥虫中发现的硫醇还原酶的抑制可能解释了观察到的选择性。高选择性和生物利用度范围内的细胞毒性浓度使 panaxynol 和其他多炔化合物成为治疗非洲锥虫病的非常有前途的先导化合物。